International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 35 - GENETIC CHARACTERIZATION OF CHAR1, A MURINE MALARIA RESISTANCE LOCUS

Ms Vikki Marshall
Walter & Eliza Hall Institute of Medical Research
Genetics & Bioinformatics Division
Royal Melbourne Hospital
Victoria 3050 Melbourne
Australia

Co-Authors: Wagglen, J, Burt RA, Baldwin TM, Templeton T, Rodda F, Senyschyn D, Allison J, Foote SJ
Institutions: The Walter & Eliza Hall Institute of Medical Research, Genetics & Bioinformatics Division, Royal Melbourne Hospital, Mouseworks, Department of Physiology, Monash University,  Department of Microbiology and Immunology, University of Melbourne

Malaria is a parasitic infection of man that is responsible for 2-3 million deaths annually. Parasite virulence and host immunological responses are important factors in survival, but other host adaptations modulate response to the parasite.

We have used the murine malaria parasite, P.chabaudi, as a model to study host control of parasite levels and survival.

Previously, we have identified a murine malaria resistance locus, char1, by analysing SJL x C57BL/6 (F2) mice. QTL analysis identified char1 as a locus contributing to peak parasitemia, and simple genotype association demonstrated linkage of the same locus to malaria-induced mortality.

We have generated several lines of char1 congenic mice which contain different B6-derived intervals, on a SJL (susceptible) background. Twenty-five percent of char1 congenic animals show a survival phenotype when challenged with P.chabaudi,  refining the char1 locus to an interval of ~2cM on distal chromosome 9.

A physical map consisting of >20 overlapping BACs and spanning a physical distance of  4Mb has been generated across the char1 locus. We are currently using BACs from this region to generate BAC transgenic lines for complementation studies, and I.V.F. technology is being used to rapidly produce large cohorts of  transgenic animals for malaria challenge. Such studies aim to further refine the char1 critical region, allowing us to identify the char1 gene and to concentrate our efforts on understanding its function.


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